Circulating microRNAs in various etiopathogenetic subtypes of acute ischemic stroke. A human systematic review study

Marina Grigolashvili¹Irina Kadyrova²Yelena Shayakhmetova¹Mira Beisembayeva¹Shynar Muratbekova¹Alina Seryogina^1*

• ¹Department of Neurology, Psychiatry and Rehabilitation, Karaganda Medical University, Karaganda, Kazakhstan
• ²Research Centre, Karaganda Medical University, Karaganda, Kazakhstan

Introduction Stroke remains one of the leading causes of death and disability among the adult population worldwide. In recent years, considerable efforts have been made to identify circulating microRNAs that could enhance the diagnostic potential of current neuroimaging techniques and assist in the differential diagnosis of distinct pathogenetic subtypes of ischemic stroke. This systematic review aimed to examine the differential expression of microRNAs (miRNAs) across various pathogenetic forms of ischemic stroke. Methods Web of Science, PubMed, and Scopus were searched for studies examining the association of circulating microRNAs with various etiologic subtypes of acute ischemic stroke. Studies meeting predefined inclusion and exclusion criteria were selected for data extraction. Two authors independently extracted data from the included studies regarding study design, patient characteristics, and relative microRNA expression. Results Twelve studies were included, involving 937 cases and 690 healthy controls. The dysregulated miRNAs (let-7b, let-7e, miR-20a, miR-125b, miR-19a, miR-30a, miR-126, etc.) may serve as non-invasive biomarkers for the diagnosis of cardioembolic stroke (CE). However, the only microRNAs associated with CE and reported in more than one study were let-7b and let-7e. The highest area under the curve (AUC) value for cases with large artery atherosclerosis (LAA) was reported for miR-16 (AUC = 0.952). During small vessel occlusion (SVO), nine circulating microRNAs were found to be differentially expressed, of which seven were downregulated and two were upregulated. Conclusion The investigation of differential microRNA expression offers significant potential for their use as biomarkers of cerebral ischemia and its etiologic subtypes. However, further research in larger patient populations is needed to validate the diagnostic utility of the identified microRNAs.